The blind men and the elephant

SEATTLE—Despite the proven value of diagnostic (Dx) testing(see sidebar, "The IVD hall of fame"), Dx testing is under-rewarded for itsrelative impact and value, says Epigenomics Inc. CEO Noel Doheny.

For example, only 4 percent of the $2.7 trillion spent onhealthcare is on Dx—despite the fact that it's responsible for 72 percent ofdiagnostic decisions, according to Doheny. In the United States, diagnosticlabs bill about $60 billion per year, and products sold to them account forabout $18 billion, against the $2.7-trillion total healthcare spend.

Epigenomics, along with its Berlin, Germany-based parentcompany Epigenomics AG, is a company focused on developing molecular diagnostictests for the early detection, prognosis, monitoring and personalized medicinein the field of cancer.

To date, cancer diagnostics are not even recognized as acategory in Scientia's recent analysis of the global in-vitro diagnostics (IVD) market, Doheny notes.

"Cancer will emerge," he predicts. "We'll see it more andmore. Today, oncology is a $250-billion-per-year healthcare crisis, and fewerthan 25 percent of patients are cured by their chemotherapy."

In particular, according to Doheny, the oft-sought goal ofpersonalized medicine (PM) is more akin to something he calls "personalizedalignment," where PM is viewed by the various participants in a way thatemulates the old adage about the blind men and the elephant. Pharma sees alikelihood of smaller markets since their drugs won't be administered on atrial-and-error basis. Payers worry about additional costs if more PM assays areapproved for payment. Physicians may see it as a tradeoff between the loss ofindividual choice and better control of the disease process. Regulators, as istheir tendency, worry about consequences they can't foresee. And to thepatient, of course, it's a matter of survival.

But Doheny is convinced the time is right to make progressat a faster clip.

"Why now?" he asks rhetorically.

Because technology has moved beyond macro level testing thatdifferentiated disease from non-disease and characterized cancer, for example,by location and size. Today, molecular-level testing predicts outcomes ofspecific therapeutics, screens for adverse events and stratifies and monitorsdisease progression. Specifically, Doheny notes, leukemia has progressed frombeing categorized as acute and chronic types and lymphoma from indolent andaggressive, to the present state of 38 identified leukemias and 51 lymphomas.

Doheny estimates that 70 percent of all new Dx technologycomes from the United States, creating an approximate $15 billion-per-yeartrade surplus. Among the "wins" lauded in the Dx "hall of fame," he points toHIV, myocardial infarction/heart attack, influenza and group-B strep.

How does a company prepare for the personalized environment?Doheny breaks it down into a 2D, 3R or 4P process: 2D, which is disease(treatable with a specific therapy) and demographic (patients and payment); 3R,which is references (peer-reviewed publications), reimbursement (third-partypayment codes) and regulation (FDA and CMS); and 4P, which is payer (understoodand accepted medical economics), provider (documented improved outcomes),patient (results that can be relied on) and pharma (behavior change).

In turn, the industry needs funding support from public andprivate sources, including venture capital, the reduction of over-regulationand a workforce of qualified technologists.

"We've got a long way to go," Doheny concludes, "but there'sa lot of opportunity."

The IVD hall of fame

Recently, Mya Thomae, founder and CEO of MYRAQA, aregulatory consulting firm for the IVD space that Noel Doheny describes as "thebest regulatory group in the world," dubbed May 2013 "Diagnostics AppreciationMonth." To mark the occasion, she and her colleagues developed a blogdescribing a "diagnostics hall of fame." Here is a greatly abbreviatedselection of six assays. The complete stories can be found at http://myraqa.com/blog/.

HIV: Viral load wasdefined as the more accurate predictor of clinical outcome. The disease, thoughnot cured, was at least under control. Long-term survival became available forthousands of HIV-positive patients.

Hepatitis B & C:The yearly incidence of HCV infection averaged more than 200,000 cases per yearin the 1980s, but by 2001, had declined to around 25,000 cases per year. As aresult of hepatitis blood screening assays, the risk of acquiring the diseasethrough a blood transfusions or organ transplant has been largely eliminated.

Lipid profiling:Monitoring of lipid panel results has allowed patients to recognize and reducetheir overall risk for cardiac disease. Statin drugs, the first of which wasapproved in the United States in 1987, are a good example of therapiesdeveloped to address control of lipid levels.

HER2/neu assay: Dakoreceived FDA approval in 1988 for the Hercep-Test, an assay used to identifypatients with HER2-positive metastatic breast cancer. These HER2-positivepatients were subsequently eligible for treatment with Genentech's Herceptin.The first FDA-approved HER2/Neu test was Ventana Medical Systems' oncor informher-2/neu gene detection system, which was approved in 1997. This assay is alsorun to select breast cancer patients for treatment with Herceptin, as well asdetermining the prognosis for patients.

Myocardial infarction (MI) panels: MI panels test for elevated levels of enzymes orproteins that are linked with injury of the heart muscle. Before MI panels wereavailable, physicians ordered each individual assay separately. As a result ofMI panels, physicians are able to obtain relevant information with one test toaid in the diagnosis of myocardial infarction.

Prenatal group B strep tests: Prior to the introduction of group B Streptococcusbacteria tests, there were higher rates of early onset group-B strep in infantswith an infant mortality rate of 55 percent for newborns. Infection was largelydue to transmission from mother to newborn at birth. The introduction ofgroup-B strep tests made it possible to identify pregnant women who carry groupB-strep and administer antibiotics during labor, thereby greatly reducing therisk of transmission to the infant.